Converging survival trends in non-small cell lung cancer patients with and without brain metastasis receiving state-of-the-art treatment.

INTRODUCTION: Historically, patients with brain metastasis (BM) have been excluded from clinical trials investigating treatments for non-small cell lung cancer (NSCLC) due to their unfavorable prognosis. Advanced treatments have increased survival prospects for NSCLC patients with BM. This study evaluated the life expectancy of NSCLC patients with and without BM in the context of contemporary treatments. METHODS: Outcome data were collected for patients with advanced NSCLC attending a tertiary medical center between 2015 and 2020. Patients were stratified according to BM status and compared for overall survival (OS) using log-rank and Cox regression analyses. RESULTS: The cohort included 360 patients with NSCLC of whom 134 (37.2%) had BM. Most (95%) of cases of BM developed within the first two years: 63% at diagnosis, 18% during the first year, 14% during the second year. There was no significant difference in OS between patients without BM and those with BM (median 23.7 vs. 22.3 months, HR = 0.97, p = 0.82); patients with BM and a targetable or non-targetable mutation (40.2 vs. 31.4 months, HR = 0.93, p = 0.84, and 20.7 vs. 19.87 months, HR = 0.95, p = 0.75, respectively); and patients with symptomatic BM (23.7 vs. 19.8 months, HR = 0.95, p = 0.78). Treatment for BM (95% of patients) consisted of stereotactic radiosurgery or tyrosine kinase inhibitors, with corresponding intracranial control rates of 90% and 86%. CONCLUSION: The results imply that the presence of BM has no impact on the prognosis of NSCLC. The practice of excluding NSCLC patients with BM from clinical trials warrants reconsideration.

Post-radiation middle ear effusion in NPC patients: Analysis of patient, tumour, and radiation factors.

OBJECTIVE: The purpose of this study was to investigate whether patient, tumour and radiation therapy factors are associated with development of middle ear effusion (MEE) in nasopharyngeal carcinoma (NPC) patients. DEIGN, SETTINGS, AND PARTICIPANTS: A retrospective review of NPC patients treated between January 2000 and June 2018 at Rabin Medical Center. Patient factors, tumour factors, radiation doses, and radiation fields were collected and outlined if needed (middle ear, eustachian tube [ET], tensor veli palatini [TVP], and levator palatini [LVP] muscles), then analysed and compared between patients with MEE and those without and between sides in patients with unilateral MEE. MAIN OUTCOME MEASURES AND RESULTS: Seventy-three patients were enrolled. Most were males (71.2%) with advanced-stage diseases (78%). At the time of diagnosis 14 patients (19.2%) presented with MEE. Following radiation, 18 patients, with no evidence of MEE at presentation, developed MEE. Tumour stage, histology, and laterality were not associated with development of MEE. Comparison of mean radiation field dosages including-gross target volume, clinical target volume, and patient target volume showed no association with post-radiation MEE. In addition, no difference was found in the radiation doses to the middle ear, ET or the LVP nor the TVP between ears with and without MEE. CONCLUSIONS: Post-irradiation MEE remains a common adverse effect in NPC patients. Surprisingly, tumour stage, tumour laterality, and histology were not associated with MEE. Similar findings were observed for total radiation doses and specific doses to the middle ear, ET, and ET muscles.

Gender-Related Aspects of Laryngeal Squamous Cell Carcinoma: A Retrospective Cohort Study.

OBJECTIVES: Laryngeal squamous cell carcinoma (SCC) is a predominantly male illness. Although the rate of female patients increased, a knowledge gap exists in the medical literature regarding gender-based differences. DESIGN: Retrospective cohort study. SETTING: Adult patients treated for laryngeal SCC in a tertiary medical centre between 2006 and 2020. Data were collected on demographics, clinical presentation, treatment modalities, disease recurrence and survival status. PARTICIPANTS: Two hundred ninety-one patients with laryngeal SCC, 50 (17.2%) females and 241 (82.8%) males. MAIN OUTCOME MEASURES: Disease-specific survival (DSS), overall survival (OS) and disease-free survival (DFS), as well as differences in disease characteristics and treatment modalities. RESULTS: Tumour subsites differed significantly between females and males (36% vs. 19.5% supraglottic, 62% vs. 80.5% glottic and 2% vs. 0% subglottic, respectively; p = 0.006). Females were diagnosed at younger ages (61.7 ± 10.58 vs. 65.87 ± 11.11 years, p = 0.016) and advanced-stage disease (58% vs. 39.4%, p = 0.018). Females were treated with combined modalities at higher rates (36% vs. 54.8% for single modality, p = 0.031). DSS rates did not differ between genders (log-rank p = 0.12). Despite being diagnosed at more advanced disease stages, females demonstrated prolonged median OS compared to males (130.17 vs. 106.17 months, log-rank p = 0.017). No significant differences in DFS were observed (log-rank p = 0.32). In a multivariate Cox proportional hazards model, male gender remained an independent negative OS predictor (HR = 2.08; CI, 1.10-3.96; p = 0.025), along with increasing age (HR = 1.06; CI, 1.04-1.09; p < 0.001) and advanced disease stage (HR = 1.7; CI, 1.08-2.67; p = 0.023). CONCLUSIONS: Our findings suggest the importance of considering gender-specific factors in the management of laryngeal SCC.

Seeing the Trees From the Forest: Challenges in Subgroup Analysis-Based Guidelines in Oncology.

As clinical trials in oncology require substantial efforts, maximizing the insights gained from them by conducting subgroup analyses is often attempted. The goal of these analyses is to identify subgroups of patients who are likely to benefit, as well as the subgroups of patients who are unlikely to benefit from the studied intervention. International guidelines occasionally include or exclude novel medications and technologies for specific subpopulations based on such analyses of pivotal trials without requiring confirmatory trials. This Perspective discusses the importance of providing a complete dataset of clinical information when reporting subgroup analyses and explains why such transparency is key for better clinical interpretation of the results and the appropriate application to clinical care, by providing examples of transparent reporting of clinical studies and examples of incomplete reporting of clinical studies.

The Clinical Behavior and Recurrence Patterns of Oral Cavity Cancer in Oral Lichen Planus Patients.

OBJECTIVES: Oral lichen planus (OLP) is a chronic inflammatory disorder involving epithelia with squamous differentiation. Although described as a potential malignant precursor, the characteristics of malignancies arising among these patients are not widely described. Our goal was to describe the patterns of disease recurrence of patients with oral cavity squamous cell carcinoma (OSCC) arising on the background of OLP. METHODS: A retrospective analysis of all surgically treated patients with OSCC at a university-affiliated tertiary care center between 2000 and 2020. RESULTS: Two hundred seventy-nine patients with OSCC treated surgically were included. Forty (14.3%) had OLP. The mean age of patients with OLP was 70.9 years compared with 64.3 years for non-OLP patients (p = 0.03). OLP patients had a significantly higher rate of disease recurrence, persistence, or multiple primary disease (70% vs. 33.9%, p < 0.001). The mean number of sequential oncologic events for each patient with recurrence was also significantly higher among OLP patients (1.86 vs. 1.36, p = 0.03), a difference explained by a higher rate of multiple primary presentations (0.71 vs. 0.28, p = 0.008). A significant difference in disease-free survival (DFS) was demonstrated between the groups as patients with OLP had a lower 5-year DFS (34.7% vs. 61.3%, log-rank p value <0.001). On multivariate analysis, OLP was significantly associated with multiple primary events (p < 0.001, Odds ratio = 7.42, 95% confidence interval 2.9-19). CONCLUSIONS: OSCC patients with OLP background demand close clinical follow-up, as multiple primary disease is significantly more common and the DFS is significantly lower among these patients. A thorough clinical evaluation for all oral cavity subsites is mandatory. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3146-3151, 2024.

Management of laryngeal chondroradionecrosis: A single-center experience.

BACKGROUND: Laryngeal chondroradionecrosis (LCRN) is a rare but severe complication of radiation therapy. The study aimed to review the management of LCRN and evaluate the clinical benefit of hyperbaric oxygen therapy (HBOT). METHODS: We retrospectively analyzed all radiation-induced LCRN patients between 2006 and 2019 at a tertiary medical center. Diagnosis was based on signs and symptoms of Chandler's classification, imaging, and/or histopathology report. The primary outcome was improvement in Chandler's grade after HBOT. RESULTS: Of 678 irradiated laryngeal cancer patients, 29 (4.3%) were diagnosed with LCRN. The most common primary management was tracheostomy with intravenous steroids and antibiotics (59%). Ten patients received HBOT (34.5%), and six underwent total laryngectomy (21%). In HBOT-treated patients, Chandler's grade significantly improved from a median of 4 (range 2-4) to 2.5 (range 1-4; p = 0.005). CONCLUSIONS: HBOT may benefit in the management of patients with persistence and unresponsive symptoms of LCRN following radiation therapy for laryngeal SCC.

Extended Follow-Up Outcomes from Pooled Prospective Studies Evaluating Efficacy of Interstitial Alpha Radionuclide Treatment for Skin and Head and Neck Cancers.

The initial favorable efficacy and safety profile for Alpha DaRT have been demonstrated (NCT04377360); however, the longer-term safety and durability of the treatment are unknown. This pooled analysis of four prospective trials evaluated the long-term safety and efficacy of Alpha DaRT for the treatment of head and neck or skin tumors. A total of 81 lesions in 71 patients were treated across six international institutions, with a median follow-up of 14.1 months (range: 2-51 months). Alpha DaRT sources were delivered via a percutaneous interstitial technique and placed to irradiate the tumor volume with the margin. The sources were removed two to three weeks following implantation. A complete response was observed in 89% of treated lesions (n = 72) and a partial response in 10% (n = 8). The two-year actuarial local recurrence-free survival was 77% [95% CI 63-87]. Variables, including recurrent versus non-recurrent lesions, baseline tumor size, or histology, did not impact long-term outcomes. Twenty-seven percent of patients developed related acute grade 2 or higher toxicities, which resolved with conservative measures. No grade 2 or higher late toxicities were observed. These data support the favorable safety profile of Alpha DaRT, which is currently being explored in a pivotal US trial.